The objective of this proposal is to investigate the interaction of cytotoxic thymus derived lymphocytes with their targets. We will explore whether the serologically detectable histocompatibility antigens are absolutely necessary for the sensitization and effector step of T cell-mediated cytotoxicity. This will be done by employing a recently isolated tumor cell line which has lost its H-2 and TL antigens. We will study the induction and effector step of cell-mediated cytotoxicity in syngeneic, allogeneic and xenogeneic models comparing this cell line with the original one which carries H-2 antigens. We will also couple the two cell lines with immunogenic molecules and infect them with virus in order to explore whether T killer cells can be sensitized to immunogenic cell surface determinants in the absence of H-2 antigens. In the second part of this proposal we will study whether coupling of ligands or viral infection lead to the expression of new or altered seriologically detectable histocompatibility antigens on the cell surface. In these experiments we will couple cells with haptens and infect them with virus and then assay the amount and specificity of SD antigens by the quantitative serum absorption procedure. If virus infection of cells causes the expression of new histocompatibility antigens on the cell surface, then we will develop a tumor model system in which protection against tumor challenge by immunization with the appropriate allogeneic cells carrying these histocompatibility antigens is accomplished.